Instability of Antibacterial Serrulatane Compounds from the Australian Plant Species Eremophila duttonii

Abstract

Hydrophilically substituted diterpenes of the structural class of serrulatanes have attracted attention as novel antibacterial compounds that are effective even against multidrug-resistant Staphylococcus aureus, a key bacterium involved in human infections. The mechanism of action has, however, not been established yet. Available data on structure–activity relationships suggest that the aromatic hydroxy group is essential for activity, and the strongest activity has been found for naphthyl compounds. In this context, it is reported that two highly active serrulatanes isolated from leaf resin of the Australian plant species Eremophila duttonii showed instability upon separation. Acetylation of hydroxy groups generated stable compounds that could be isolated and identified by NMR spectroscopy. The acetylated compounds showed little antibacterial activity, but such activity, as well as oxidative instability, was restored after hydrolysis of the acetate groups. Thus, phenolic hydroxy groups are essential for the mechanism of action of these compounds. The reaction products were not purifiable in sufficient quantities, but indications point to oxidation to quinones. Such oxidation may be a key aspect of the antibacterial activity of this class of compounds.